QUADRA: A Study of Niraparib in Patients With Ovarian Cancer Who Have Received Three or Four Previous Chemotherapy Regimens

• Sponsor: Tesaro, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02354586
• Collaborator: Facing Our Risk of Cancer Empowered (Other), Myriad Genetics, Inc. (Industry)
• Enrollment: 463
• Locations: 55
• Arm: 1
• Actual Duration (Months): 77
• Patients Per Site: 8.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a Phase 2, open-label, single arm study to evaluate the safety and efficacy of niraparib in ovarian cancer patients who have received three or four previous chemotherapy regimens. Niraparib is an orally active PARP inhibitor. Niraparib will be administered once daily continuously during a 28-day cycle. Health-related quality of life will be measured by Eastern Cooperative Oncology Group performance status (ECOG). Safety and tolerability will be assessed by clinical review of adverse events (AEs), physical examinations, electrocardiograms (ECGs), RECIST tumor assessments and safety laboratory values.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Neoplasms; Ovarian Cancer	Drug: Niraparib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 463 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of Niraparib in Patients With Advanced, Relapsed, High-Grade Serous Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Have Received Three or Four Previous Chemotherapy Regimens
• Actual Study Start Date: Mar 23, 2015
• Actual Primary Completion Date: Feb 28, 2018
• Actual Study Completion Date: Aug 23, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Niraparib	Drug: Niraparib

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) [Up to 3 years]

   The ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) (version1.1). Primary Analysis Population comprised of participants who received 3 or 4 prior lines of therapy (LOT), had homologous recombination deficiency positive (HRDpos) tumors, had platinum-sensitive disease, and were poly(adenosine 5'-diphosphate [ADP]-ribose) polymerase inhibitors (PARPi) naïve.

Secondary Outcome Measures

1. Duration of Response (DoR) [Up to 3 years]

   DoR was defined as the time from first documentation of CR or PR until the time of first documentation of disease progression (PD) as assessed by the Investigator per RECIST (version1.1). DoR was analyzed using Kaplan-Meier (KM) method.

2. ORR by HRD Status and Breast Cancer Gene (BRCA) Status [Up to 3 years]

   The ORR was defined as the percentage of participants achieving CR or PR as assessed by the Investigator per RECIST (version1.1). ORR was evaluated for participants with following characteristics: HRD status (positive, negative and unknown) and BRCA status (mutation positive, wild-type and unknown).

3. Disease Control Rate (DCR) [Up to 3 years]

   Disease control rate was defined as the percentage of participants achieving CR, PR, or stable disease (SD) as assessed by the Investigator per RECIST (version1.1). The exact (Clopper-Pearson) method was used to calculate 95% confidence interval.

4. Progression Free Survival [Up to 3 years]

   Progression-free survival was defined as the time from the date of first dose to the earlier date of assessment of progression or death by any cause in the absence of progression as assessed by the Investigator per RECIST (version 1.1) or clinical criteria.

5. Overall Survival [Up to 3 years]

   Overall Survival was defined as the time from the date of the first dose to the date of death by any cause. It was calculated as [Date of Death minus First dose date plus 1] divided by 30.4375.

6. Time to First Subsequent Therapy (TFST) [Up to 3 years]

   Time to first subsequent therapy (TFST) was defined as the time from the date of first dose to the date of first subsequent therapy or death, whichever occurs first. It was calculated as (Earlier of [First dose of first subsequent therapy or death] minus First dose date plus 1) divided by 30.4375.

Other Outcome Measures

1. Number of Participants With Any Non-serious Adverse Event (Non-SAE) or Any SAE [Up to 3 years]

   An adverse event is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE.

2. Number of Participants With Abnormality in Hematology Parameters [Up to 3 years]

   Number of participants with abnormality in hematology parameters were planned to be analyzed.

3. Number of Participants With Abnormality in Clinical Chemistry Parameters [Up to 3 years]

   Number of participants with abnormality in clinical chemistry parameters were planned to be analyzed.

4. Number of Participants With Abnormality in Vital Signs [Up to 3 years]

   Number of participants with abnormality in vital signs were planned to be analyzed.

5. Number of Participants With Abnormality in Physical Examination [Up to 3 years]

   Number of participants with abnormality in physical examination were planned to be analyzed.

6. Number of Participants Who Were Administered Concomitant Medications [Up to 3 years]

   Number of participants who were administered concomitant medications were planned to be analyzed.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must agree to undergo tumor HRD testing and blood gBRCAmut status testing.

• Patients of childbearing potential must have negative pregnancy serum test within 72 hours of being dosed

• Patients must have histologically diagnosed high-grade (Grade 2 or 3) serous epithelial ovarian, fallopian tube, or primary peritoneal cancer with recurrent disease and must have been previously treated with chemotherapy and experienced a response lasting at least 6 months to first-line platinum based therapy.

• Patients Must have completed 3 or 4 previous chemotherapy regimens.

• Patients must have completed their last chemotherapy regimen > 4 weeks prior to treatment initiation.

• Patients must have measurable disease according to RECIST (v.1.1).

• Patients must have formalin-fixed, paraffin-embedded tumor samples available from the primary or recurrent cancer or agree to undergo fresh biopsy prior to study treatment initiation.

• Patients must agree to blood samples during screening and at the end of treatment for cytogenetic analysis.

Exclusion Criteria:

• Patients must not have any known, persistent (> 4 weeks), ≥Grade 3 hematologic toxicity during the last cancer therapy. Patients must not have any known, persistent (>4 weeks), ≥ Grade 3 fatigue during the last cancer therapy.

• Patients must not have received pelvic radiotherapy as treatment for primary or recurrent disease within 1 year of the first dose of study treatment.

• Patients must not have symptomatic uncontrolled brain or leptomeningeal metastases.

• Patients must not be considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active, uncontrolled infection.

• Patients must not have received a transfusion (platelets or red blood cells) within 4 weeks of the first dose of study treatment.

• Patients must not have known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Chandler	Arizona	United States	85224
2	GSK Investigational Site	Phoenix	Arizona	United States	85016
3	GSK Investigational Site	Tucson	Arizona	United States	85710
4	GSK Investigational Site	Burbank	California	United States	91505
5	GSK Investigational Site	Duarte	California	United States	91010
6	GSK Investigational Site	Los Angeles	California	United States	90027
7	GSK Investigational Site	Los Angeles	California	United States	90048
8	GSK Investigational Site	San Francisco	California	United States	94118
9	GSK Investigational Site	Santa Barbara	California	United States	93105
10	GSK Investigational Site	Stanford	California	United States	94305-5317
11	GSK Investigational Site	New Haven	Connecticut	United States	06510
12	GSK Investigational Site	Tampa	Florida	United States	33612
13	GSK Investigational Site	West Palm Beach	Florida	United States	33401
14	GSK Investigational Site	Atlanta	Georgia	United States	30342
15	GSK Investigational Site	Chicago	Illinois	United States	60611
16	GSK Investigational Site	Chicago	Illinois	United States	60637
17	GSK Investigational Site	Indianapolis	Indiana	United States	46260
18	GSK Investigational Site	Indianapolis	Indiana	United States	54244
19	GSK Investigational Site	Covington	Louisiana	United States	70433
20	GSK Investigational Site	New Orleans	Louisiana	United States	70121
21	GSK Investigational Site	Baltimore	Maryland	United States	21202
22	GSK Investigational Site	Boston	Massachusetts	United States	02115
23	GSK Investigational Site	Boston	Massachusetts	United States	02215
24	GSK Investigational Site	Burlington	Massachusetts	United States	01805
25	GSK Investigational Site	Ann Arbor	Michigan	United States	48109
26	GSK Investigational Site	Minneapolis	Minnesota	United States	55455
27	GSK Investigational Site	Rochester	Minnesota	United States	55905
28	GSK Investigational Site	Springfield	Missouri	United States	65804
29	GSK Investigational Site	Hackensack	New Jersey	United States	07601
30	GSK Investigational Site	Morristown	New Jersey	United States	07962-1956
31	GSK Investigational Site	East Setauket	New York	United States	11733
32	GSK Investigational Site	Jamaica	New York	United States	11432
33	GSK Investigational Site	Lake Success	New York	United States	11042
34	GSK Investigational Site	New York	New York	United States	10065
35	GSK Investigational Site	Durham	North Carolina	United States	27710
36	GSK Investigational Site	Oklahoma City	Oklahoma	United States	73104
37	GSK Investigational Site	Medford	Oregon	United States	97504-8342
38	GSK Investigational Site	Wynnewood	Pennsylvania	United States	19096
39	GSK Investigational Site	Providence	Rhode Island	United States	02905
40	GSK Investigational Site	Nashville	Tennessee	United States	37203
41	GSK Investigational Site	Austin	Texas	United States	78731
42	GSK Investigational Site	Dallas	Texas	United States	75390
43	GSK Investigational Site	Fort Worth	Texas	United States	76104
44	GSK Investigational Site	San Antonio	Texas	United States	78229
45	GSK Investigational Site	The Woodlands	Texas	United States	77380
46	GSK Investigational Site	Tyler	Texas	United States	75702
47	GSK Investigational Site	Spokane	Washington	United States	99202
48	GSK Investigational Site	Tacoma	Washington	United States	98405
49	GSK Investigational Site	Calgary	Alberta	Canada	T2N 4N2
50	GSK Investigational Site	Toronto	Ontario	Canada	M5G 2M9
51	GSK Investigational Site	Montreal	Quebec	Canada	H1T 2M4
52	GSK Investigational Site	Montreal	Quebec	Canada	H2L 4M1
53	GSK Investigational Site	Montreal	Quebec	Canada	H3T 1E2
54	GSK Investigational Site	Montreal	Quebec	Canada	H4A 3J1
55	GSK Investigational Site	Sherbrooke	Quebec	Canada	J1H 5N4

Sponsors and Collaborators

• Tesaro, Inc.
• Facing Our Risk of Cancer Empowered
• Myriad Genetics, Inc.

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Dec 21, 2017
• Statistical Analysis Plan - Dec 11, 2018

More Information

Publications

• Moore KN, Secord AA, Geller MA, Miller DS, Cloven N, Fleming GF, Wahner Hendrickson AE, Azodi M, DiSilvestro P, Oza AM, Cristea M, Berek JS, Chan JK, Rimel BJ, Matei DE, Li Y, Sun K, Luptakova K, Matulonis UA, Monk BJ. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019 May;20(5):636-648. doi: 10.1016/S1470-2045(19)30029-4. Epub 2019 Apr 1. Erratum in: Lancet Oncol. 2019 May;20(5):e242.

• Responsible Party: Tesaro, Inc.
• ClinicalTrials.gov Identifier: NCT02354586
• Other Study ID Numbers: 213360; PR-30-5020-C
• First Posted: Feb 3, 2015
• Last Update Posted: Oct 21, 2021
• Last Verified: Sep 1, 2021

• Keywords provided by Tesaro, Inc.: gBRCAmut; BRCA; PARP inhibitor; HRD; Ovarian cancer; Serous Epithelial; Fallopian Tube; Primary Peritoneal
• Additional relevant MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Niraparib

Study Results

Participant Flow

Recruitment Details	This was a Phase 2, open-label, single arm study to evaluate the safety and efficacy of niraparib in ovarian cancer participants who have received three or four previous chemotherapy regimens. The results of the study are based on primary analysis (up to 3 years).
Pre-assignment Detail	A total of 729 participants were screened, of which 463 participants received study treatment, niraparib.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Participants received Niraparib (300 milligram [mg], taken as 3 capsules of 100 mg once daily [QD]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Period Title: Overall Study
STARTED	463
Ongoing in Study	21
COMPLETED	122
NOT COMPLETED	341

Baseline Characteristics

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Participants received Niraparib (300 milligram [mg], taken as 3 capsules of 100 mg once daily [QD]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Overall Participants	463
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	64.3 (9.28)
Sex: Female, Male (Count of Participants)
Female	463 100%
Male	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	394 85.1%
Black	20 4.3%
Asian	16 3.5%
American Indian or Alaska Native	1 0.2%
Unknown	32 6.9%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
Description	The ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) (version1.1). Primary Analysis Population comprised of participants who received 3 or 4 prior lines of therapy (LOT), had homologous recombination deficiency positive (HRDpos) tumors, had platinum-sensitive disease, and were poly(adenosine 5'-diphosphate [ADP]-ribose) polymerase inhibitors (PARPi) naïve.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Primary Analysis Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Participants received Niraparib (300 milligram [mg], taken as 3 capsules of 100 mg once daily [QD]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Measure Participants	47
Number (95% Confidence Interval) [Percentage of participants]	27.66 6%

2. Secondary Outcome

Title	Duration of Response (DoR)
Description	DoR was defined as the time from first documentation of CR or PR until the time of first documentation of disease progression (PD) as assessed by the Investigator per RECIST (version1.1). DoR was analyzed using Kaplan-Meier (KM) method.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population was comprised of all dosed participants with measurable disease at Baseline. Measurable disease at Baseline was determined by the existence of at least 1 target lesion at Baseline tumor scan based on investigator's assessment. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Participants received Niraparib (300 milligram [mg], taken as 3 capsules of 100 mg once daily [QD]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Measure Participants	39
Median (95% Confidence Interval) [Months]	9.4

3. Secondary Outcome

Title	ORR by HRD Status and Breast Cancer Gene (BRCA) Status
Description	The ORR was defined as the percentage of participants achieving CR or PR as assessed by the Investigator per RECIST (version1.1). ORR was evaluated for participants with following characteristics: HRD status (positive, negative and unknown) and BRCA status (mutation positive, wild-type and unknown).
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

ITT Population. All the participants from the ITT Population were analyzed (461 participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Participants received Niraparib (300 milligram [mg], taken as 3 capsules of 100 mg once daily [QD]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Measure Participants	461
HRD positive, n=221	14.0 3%
HRD negative, n=195	2.6 0.6%
HRD unknown, n=45	6.7 1.4%
BRCA mutation positive, n=87	23.0 5%
BRCA wild-type, n=317	5.0 1.1%
BRCA unknown, n=57	5.3 1.1%

4. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	Disease control rate was defined as the percentage of participants achieving CR, PR, or stable disease (SD) as assessed by the Investigator per RECIST (version1.1). The exact (Clopper-Pearson) method was used to calculate 95% confidence interval.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Participants received Niraparib (300 milligram [mg], taken as 3 capsules of 100 mg once daily [QD]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Measure Participants	461
Number (95% Confidence Interval) [Percentage of participants]	49.02 10.6%

5. Secondary Outcome

Title	Progression Free Survival
Description	Progression-free survival was defined as the time from the date of first dose to the earlier date of assessment of progression or death by any cause in the absence of progression as assessed by the Investigator per RECIST (version 1.1) or clinical criteria.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Participants received Niraparib (300 milligram [mg], taken as 3 capsules of 100 mg once daily [QD]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Measure Participants	461
Median (95% Confidence Interval) [Months]	3.5

6. Secondary Outcome

Title	Overall Survival
Description	Overall Survival was defined as the time from the date of the first dose to the date of death by any cause. It was calculated as [Date of Death minus First dose date plus 1] divided by 30.4375.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Participants received Niraparib (300 milligram [mg], taken as 3 capsules of 100 mg once daily [QD]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Measure Participants	461
Median (95% Confidence Interval) [Months]	17.2

7. Secondary Outcome

Title	Time to First Subsequent Therapy (TFST)
Description	Time to first subsequent therapy (TFST) was defined as the time from the date of first dose to the date of first subsequent therapy or death, whichever occurs first. It was calculated as (Earlier of [First dose of first subsequent therapy or death] minus First dose date plus 1) divided by 30.4375.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Participants received Niraparib (300 milligram [mg], taken as 3 capsules of 100 mg once daily [QD]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Measure Participants	461
Median (95% Confidence Interval) [Months]	6.8

8. Other Pre-specified Outcome

Title	Number of Participants With Any Non-serious Adverse Event (Non-SAE) or Any SAE
Description	An adverse event is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Safety population was defined as all participants who received at least one dose of study drug.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Participants received Niraparib (300 milligram [mg], taken as 3 capsules of 100 mg once daily [QD]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Measure Participants	463
Any non-SAE	461 99.6%
Any SAE	197 42.5%

9. Other Pre-specified Outcome

Title	Number of Participants With Abnormality in Hematology Parameters
Description	Number of participants with abnormality in hematology parameters were planned to be analyzed.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Safety population. This was an other pre-specified outcome measure. Data will not be analyzed and reported.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Participants received Niraparib (300 milligram [mg], taken as 3 capsules of 100 mg once daily [QD]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Measure Participants	0

10. Other Pre-specified Outcome

Title	Number of Participants With Abnormality in Clinical Chemistry Parameters
Description	Number of participants with abnormality in clinical chemistry parameters were planned to be analyzed.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Safety population. This was an other pre-specified outcome measure. Data will not be analyzed and reported.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Participants received Niraparib (300 milligram [mg], taken as 3 capsules of 100 mg once daily [QD]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Measure Participants	0

11. Other Pre-specified Outcome

Title	Number of Participants With Abnormality in Vital Signs
Description	Number of participants with abnormality in vital signs were planned to be analyzed.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Safety population. This was an other pre-specified outcome measure. Data will not be analyzed and reported.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Participants received Niraparib (300 milligram [mg], taken as 3 capsules of 100 mg once daily [QD]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Measure Participants	0

12. Other Pre-specified Outcome

Title	Number of Participants With Abnormality in Physical Examination
Description	Number of participants with abnormality in physical examination were planned to be analyzed.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Safety population. This was an other pre-specified outcome measure. Data will not be analyzed and reported.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Participants received Niraparib (300 milligram [mg], taken as 3 capsules of 100 mg once daily [QD]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Measure Participants	0

13. Other Pre-specified Outcome

Title	Number of Participants Who Were Administered Concomitant Medications
Description	Number of participants who were administered concomitant medications were planned to be analyzed.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Safety population. This was an other pre-specified outcome measure. Data will not be analyzed and reported.

Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Participants received Niraparib (300 milligram [mg], taken as 3 capsules of 100 mg once daily [QD]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
Measure Participants	0

Adverse Events

Time Frame	Non-SAEs and SAEs were reported from start of study treatment and up to 3 years
Adverse Event Reporting Description	Non-SAEs and SAEs were reported for Safety Population.
Arm/Group Title	Niraparib 300 mg
Arm/Group Description	Participants received Niraparib (300 milligram [mg], taken as 3 capsules of 100 mg once daily [QD]) orally beginning on Day 1 of every cycle (28 days) until treatment discontinuation.
All Cause Mortality
	Niraparib 300 mg
	Affected / at Risk (%)	# Events
Total	170/463 (36.7%)
Serious Adverse Events
	Niraparib 300 mg
	Affected / at Risk (%)	# Events
Total	197/463 (42.5%)
Blood and lymphatic system disorders
Anaemia	15/463 (3.2%)	21
Bone marrow failure	1/463 (0.2%)	1
Leukopenia	3/463 (0.6%)	9
Lymphopenia	3/463 (0.6%)	3
Neutropenia	11/463 (2.4%)	19
Normochromic normocytic anaemia	1/463 (0.2%)	1
Pancytopenia	2/463 (0.4%)	2
Thrombocytopenia	34/463 (7.3%)	72
Cardiac disorders
Arrhythmia supraventricular	1/463 (0.2%)	1
Atrial fibrillation	1/463 (0.2%)	1
Cardiac arrest	2/463 (0.4%)	2
Cardiopulmonary failure	1/463 (0.2%)	1
Myocardial infarction	1/463 (0.2%)	1
Palpitations	2/463 (0.4%)	2
Pericardial effusion	1/463 (0.2%)	1
Supraventricular tachycardia	1/463 (0.2%)	1
Tachycardia	1/463 (0.2%)	1
Eye disorders
Retinal tear	1/463 (0.2%)	1
Vitreous haemorrhage	1/463 (0.2%)	1
Gastrointestinal disorders
Abdominal discomfort	1/463 (0.2%)	1
Abdominal distension	1/463 (0.2%)	1
Abdominal pain	17/463 (3.7%)	17
Abdominal pain upper	1/463 (0.2%)	1
Ascites	4/463 (0.9%)	4
Colitis	1/463 (0.2%)	1
Constipation	10/463 (2.2%)	10
Diarrhoea	1/463 (0.2%)	1
Dysphagia	2/463 (0.4%)	2
Enteritis	1/463 (0.2%)	1
Erosive oesophagitis	1/463 (0.2%)	1
Gastric haemorrhage	1/463 (0.2%)	1
Gastritis	1/463 (0.2%)	1
Gastrointestinal fistula	1/463 (0.2%)	1
Ileus	2/463 (0.4%)	2
Intestinal obstruction	8/463 (1.7%)	8
Intestinal perforation	1/463 (0.2%)	1
Large intestinal obstruction	2/463 (0.4%)	2
Nausea	21/463 (4.5%)	23
Obstruction gastric	1/463 (0.2%)	1
Oesophageal varices haemorrhage	1/463 (0.2%)	2
Oesophagitis	1/463 (0.2%)	1
Rectal haemorrhage	2/463 (0.4%)	2
Small intestinal obstruction	34/463 (7.3%)	43
Stomatitis	1/463 (0.2%)	1
Vomiting	27/463 (5.8%)	32
General disorders
Asthenia	3/463 (0.6%)	3
Chest pain	2/463 (0.4%)	2
Fatigue	2/463 (0.4%)	2
Mucosal inflammation	1/463 (0.2%)	1
Pain	1/463 (0.2%)	1
Pyrexia	6/463 (1.3%)	6
Strangulated hernia	1/463 (0.2%)	1
Sudden death	1/463 (0.2%)	1
Hepatobiliary disorders
Acute hepatic failure	1/463 (0.2%)	1
Biliary tract disorder	1/463 (0.2%)	1
Cholangitis	1/463 (0.2%)	1
Hepatic failure	1/463 (0.2%)	1
Hyperbilirubinaemia	1/463 (0.2%)	1
Infections and infestations
Bacteraemia	1/463 (0.2%)	1
Bronchitis	1/463 (0.2%)	1
Escherichia urinary tract infection	1/463 (0.2%)	1
Gastroenteritis	1/463 (0.2%)	1
Gastroenteritis viral	1/463 (0.2%)	1
Influenza	1/463 (0.2%)	1
Joint abscess	1/463 (0.2%)	2
Liver abscess	1/463 (0.2%)	1
Osteomyelitis	1/463 (0.2%)	1
Pharyngitis streptococcal	1/463 (0.2%)	1
Pneumonia	1/463 (0.2%)	1
Pyelonephritis	1/463 (0.2%)	1
Sepsis	8/463 (1.7%)	9
Streptococcal bacteraemia	1/463 (0.2%)	1
Upper respiratory tract infection	1/463 (0.2%)	1
Urinary tract infection	3/463 (0.6%)	3
Wound infection	1/463 (0.2%)	1
Injury, poisoning and procedural complications
Gastrointestinal stoma complication	1/463 (0.2%)	1
Overdose	1/463 (0.2%)	1
Subdural haematoma	1/463 (0.2%)	1
Investigations
Blood creatinine increased	2/463 (0.4%)	3
Electrocardiogram QT prolonged	1/463 (0.2%)	1
Gamma-glutamyltransferase increased	1/463 (0.2%)	2
Haemoglobin decreased	1/463 (0.2%)	1
Neutrophil count decreased	2/463 (0.4%)	3
Platelet count decreased	7/463 (1.5%)	20
Metabolism and nutrition disorders
Dehydration	8/463 (1.7%)	9
Electrolyte imbalance	2/463 (0.4%)	2
Hypocalcaemia	1/463 (0.2%)	1
Hypokalaemia	2/463 (0.4%)	2
Hyponatraemia	3/463 (0.6%)	4
Hypophagia	1/463 (0.2%)	1
Musculoskeletal and connective tissue disorders
Back pain	3/463 (0.6%)	3
Flank pain	2/463 (0.4%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	1/463 (0.2%)	1
Breast cancer	1/463 (0.2%)	1
Breast cancer recurrent	1/463 (0.2%)	1
Cancer pain	2/463 (0.4%)	2
Malignant pleural effusion	2/463 (0.4%)	2
Myelodysplastic syndrome	1/463 (0.2%)	1
Nervous system disorders
Headache	1/463 (0.2%)	1
Seizure	1/463 (0.2%)	1
Status epilepticus	1/463 (0.2%)	1
Transient global amnesia	1/463 (0.2%)	1
Transient ischaemic attack	1/463 (0.2%)	1
Psychiatric disorders
Mental status changes	1/463 (0.2%)	1
Suicidal ideation	1/463 (0.2%)	1
Renal and urinary disorders
Acute kidney injury	2/463 (0.4%)	2
Haematuria	1/463 (0.2%)	1
Hydronephrosis	2/463 (0.4%)	2
Nephrolithiasis	2/463 (0.4%)	2
Ureteric obstruction	1/463 (0.2%)	1
Urinary tract obstruction	1/463 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	2/463 (0.4%)	2
Chronic obstructive pulmonary disease	1/463 (0.2%)	1
Dyspnoea	6/463 (1.3%)	6
Hypoxia	1/463 (0.2%)	1
Pleural effusion	8/463 (1.7%)	10
Pneumothorax	1/463 (0.2%)	1
Pulmonary embolism	1/463 (0.2%)	1
Respiratory failure	1/463 (0.2%)	1
Vascular disorders
Deep vein thrombosis	4/463 (0.9%)	4
Embolism	1/463 (0.2%)	1
Hypertension	8/463 (1.7%)	8
Hypotension	1/463 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Niraparib 300 mg
	Affected / at Risk (%)	# Events
Total	461/463 (99.6%)
Blood and lymphatic system disorders
Anaemia	227/463 (49%)	652
Anaemia macrocytic	1/463 (0.2%)	1
Aplastic anaemia	1/463 (0.2%)	1
Increased tendency to bruise	3/463 (0.6%)	3
Leukocytosis	2/463 (0.4%)	2
Leukopenia	31/463 (6.7%)	72
Lymph node pain	4/463 (0.9%)	4
Lymphadenopathy	1/463 (0.2%)	1
Lymphocytosis	1/463 (0.2%)	1
Lymphopenia	14/463 (3%)	33
Neutropenia	49/463 (10.6%)	98
Neutrophilia	1/463 (0.2%)	1
Pancytopenia	1/463 (0.2%)	1
Thrombocytopenia	151/463 (32.6%)	410
Thrombocytosis	1/463 (0.2%)	1
Cardiac disorders
Angina pectoris	3/463 (0.6%)	3
Atrial fibrillation	5/463 (1.1%)	6
Atrial flutter	1/463 (0.2%)	1
Atrioventricular block first degree	1/463 (0.2%)	1
Extrasystoles	1/463 (0.2%)	1
Left atrial enlargement	2/463 (0.4%)	2
Myocardial infarction	2/463 (0.4%)	2
Palpitations	32/463 (6.9%)	37
Pericardial effusion	2/463 (0.4%)	2
Sinus tachycardia	14/463 (3%)	17
Tachycardia	15/463 (3.2%)	19
Ventricular arrhythmia	1/463 (0.2%)	1
Ventricular extrasystoles	3/463 (0.6%)	3
Ear and labyrinth disorders
Auditory disorder	1/463 (0.2%)	1
Ear congestion	2/463 (0.4%)	2
Ear discomfort	1/463 (0.2%)	1
Ear pain	5/463 (1.1%)	5
Middle ear inflammation	1/463 (0.2%)	1
Tinnitus	3/463 (0.6%)	3
Vertigo	4/463 (0.9%)	4
Vestibular disorder	1/463 (0.2%)	1
Endocrine disorders
Hyperthyroidism	1/463 (0.2%)	1
Hypothyroidism	2/463 (0.4%)	2
Eye disorders
Abnormal sensation in eye	1/463 (0.2%)	2
Age-related macular degeneration	1/463 (0.2%)	1
Asthenopia	1/463 (0.2%)	1
Cataract	2/463 (0.4%)	3
Corneal disorder	1/463 (0.2%)	1
Diplopia	3/463 (0.6%)	3
Dry eye	2/463 (0.4%)	2
Eye disorder	1/463 (0.2%)	1
Lacrimation increased	2/463 (0.4%)	2
Night blindness	1/463 (0.2%)	1
Ocular hyperaemia	1/463 (0.2%)	1
Photophobia	2/463 (0.4%)	2
Photopsia	1/463 (0.2%)	1
Vision blurred	6/463 (1.3%)	6
Visual impairment	3/463 (0.6%)	3
Vitreous floaters	1/463 (0.2%)	1
Gastrointestinal disorders
Abdominal discomfort	9/463 (1.9%)	12
Abdominal distension	60/463 (13%)	78
Abdominal hernia	1/463 (0.2%)	1
Abdominal pain	85/463 (18.4%)	122
Abdominal pain lower	8/463 (1.7%)	8
Abdominal pain upper	24/463 (5.2%)	25
Anal fissure	1/463 (0.2%)	1
Anal haemorrhage	1/463 (0.2%)	1
Anal incontinence	1/463 (0.2%)	1
Anorectal discomfort	1/463 (0.2%)	1
Aphthous ulcer	1/463 (0.2%)	1
Ascites	12/463 (2.6%)	15
Colitis	1/463 (0.2%)	1
Constipation	153/463 (33%)	191
Defaecation urgency	1/463 (0.2%)	1
Dental caries	3/463 (0.6%)	3
Diarrhoea	76/463 (16.4%)	95
Dry mouth	23/463 (5%)	24
Dyschezia	1/463 (0.2%)	1
Dyspepsia	33/463 (7.1%)	34
Dysphagia	6/463 (1.3%)	9
Epigastric discomfort	1/463 (0.2%)	1
Erosive oesophagitis	1/463 (0.2%)	1
Eructation	4/463 (0.9%)	4
Faeces discoloured	1/463 (0.2%)	1
Faeces hard	1/463 (0.2%)	1
Faeces soft	1/463 (0.2%)	1
Flatulence	14/463 (3%)	16
Gastric varices	1/463 (0.2%)	1
Gastrointestinal pain	1/463 (0.2%)	1
Gastrooesophageal reflux disease	25/463 (5.4%)	31
Gingival bleeding	2/463 (0.4%)	2
Haematemesis	2/463 (0.4%)	3
Haematochezia	3/463 (0.6%)	3
Haemorrhoids	4/463 (0.9%)	4
Hypoaesthesia oral	2/463 (0.4%)	2
Impaired gastric emptying	1/463 (0.2%)	1
Intestinal obstruction	3/463 (0.6%)	3
Large intestinal obstruction	4/463 (0.9%)	4
Lip oedema	1/463 (0.2%)	1
Mouth haemorrhage	1/463 (0.2%)	1
Mouth swelling	1/463 (0.2%)	1
Nausea	304/463 (65.7%)	428
Obstruction gastric	1/463 (0.2%)	1
Odynophagia	2/463 (0.4%)	2
Oesophageal pain	1/463 (0.2%)	1
Oesophagitis	4/463 (0.9%)	5
Oral mucosal erythema	1/463 (0.2%)	1
Oral pain	3/463 (0.6%)	3
Paraesthesia oral	1/463 (0.2%)	2
Proctalgia	2/463 (0.4%)	3
Rectal haemorrhage	6/463 (1.3%)	6
Rectal obstruction	1/463 (0.2%)	1
Rectal spasm	1/463 (0.2%)	1
Retching	7/463 (1.5%)	7
Salivary hypersecretion	1/463 (0.2%)	1
Small intestinal obstruction	4/463 (0.9%)	6
Stomatitis	37/463 (8%)	42
Swollen tongue	1/463 (0.2%)	1
Tongue disorder	1/463 (0.2%)	1
Toothache	2/463 (0.4%)	2
Vomiting	195/463 (42.1%)	292
General disorders
Asthenia	29/463 (6.3%)	35
Axillary pain	1/463 (0.2%)	1
Chest discomfort	2/463 (0.4%)	2
Chest pain	1/463 (0.2%)	1
Chills	12/463 (2.6%)	12
Drug withdrawal syndrome	1/463 (0.2%)	1
Early satiety	11/463 (2.4%)	11
Energy increased	1/463 (0.2%)	1
Face oedema	1/463 (0.2%)	1
Facial pain	1/463 (0.2%)	1
Fatigue	236/463 (51%)	334
Feeling jittery	2/463 (0.4%)	2
Gait disturbance	2/463 (0.4%)	2
Influenza like illness	7/463 (1.5%)	9
Injection site pain	1/463 (0.2%)	1
Local swelling	1/463 (0.2%)	1
Localised oedema	2/463 (0.4%)	3
Malaise	6/463 (1.3%)	6
Medical device pain	1/463 (0.2%)	1
Mucosal inflammation	13/463 (2.8%)	21
Non-cardiac chest pain	6/463 (1.3%)	8
Oedema	3/463 (0.6%)	3
Oedema peripheral	29/463 (6.3%)	30
Pain	9/463 (1.9%)	10
Performance status decreased	1/463 (0.2%)	1
Peripheral swelling	10/463 (2.2%)	12
Pyrexia	20/463 (4.3%)	22
Suprapubic pain	1/463 (0.2%)	1
Temperature intolerance	1/463 (0.2%)	1
Tenderness	1/463 (0.2%)	1
Thirst	2/463 (0.4%)	2
Hepatobiliary disorders
Cholecystitis	1/463 (0.2%)	1
Cholelithiasis	2/463 (0.4%)	2
Immune system disorders
Drug hypersensitivity	1/463 (0.2%)	1
Hypersensitivity	1/463 (0.2%)	1
Seasonal allergy	7/463 (1.5%)	7
Infections and infestations
Abdominal abscess	1/463 (0.2%)	2
Bacteraemia	1/463 (0.2%)	1
Beta haemolytic streptococcal infection	1/463 (0.2%)	1
Bronchitis	5/463 (1.1%)	5
Candida infection	3/463 (0.6%)	3
Cellulitis	2/463 (0.4%)	2
Chronic sinusitis	2/463 (0.4%)	2
Clostridium difficile infection	1/463 (0.2%)	1
Conjunctivitis viral	1/463 (0.2%)	1
Cystitis	1/463 (0.2%)	1
Ear infection	2/463 (0.4%)	2
Eye infection	1/463 (0.2%)	1
Folliculitis	1/463 (0.2%)	1
Gingivitis	1/463 (0.2%)	1
Hepatitis viral	1/463 (0.2%)	1
Herpes zoster	8/463 (1.7%)	8
Infected cyst	1/463 (0.2%)	1
Influenza	4/463 (0.9%)	4
Laryngitis	3/463 (0.6%)	3
Localised infection	1/463 (0.2%)	1
Lower respiratory tract infection	1/463 (0.2%)	1
Lung infection	1/463 (0.2%)	1
Oesophageal candidiasis	1/463 (0.2%)	1
Oral candidiasis	1/463 (0.2%)	1
Oral herpes	3/463 (0.6%)	3
Paronychia	1/463 (0.2%)	1
Pharyngitis streptococcal	1/463 (0.2%)	1
Pneumonia	6/463 (1.3%)	6
Pyelonephritis	2/463 (0.4%)	2
Rhinitis	2/463 (0.4%)	2
Sepsis	1/463 (0.2%)	1
Sinusitis	12/463 (2.6%)	14
Tinea pedis	1/463 (0.2%)	1
Tooth infection	2/463 (0.4%)	3
Upper respiratory tract infection	12/463 (2.6%)	16
Urinary tract infection	61/463 (13.2%)	79
Viral infection	2/463 (0.4%)	2
Viral upper respiratory tract infection	14/463 (3%)	19
Vulvovaginal mycotic infection	1/463 (0.2%)	1
Injury, poisoning and procedural complications
Ankle fracture	1/463 (0.2%)	1
Arthropod bite	3/463 (0.6%)	3
Contusion	11/463 (2.4%)	11
Ear canal abrasion	1/463 (0.2%)	1
Facial bones fracture	1/463 (0.2%)	1
Fall	5/463 (1.1%)	5
Foot fracture	1/463 (0.2%)	1
Gastrointestinal stoma complication	1/463 (0.2%)	1
Hand fracture	1/463 (0.2%)	1
Head injury	1/463 (0.2%)	1
Incisional hernia	1/463 (0.2%)	1
Laceration	1/463 (0.2%)	1
Muscle strain	1/463 (0.2%)	1
Post-traumatic pain	1/463 (0.2%)	1
Procedural pain	1/463 (0.2%)	1
Radiation skin injury	1/463 (0.2%)	2
Rib fracture	2/463 (0.4%)	2
Subarachnoid haemorrhage	1/463 (0.2%)	1
Subdural haematoma	1/463 (0.2%)	1
Sunburn	1/463 (0.2%)	1
Thermal burn	1/463 (0.2%)	1
Tooth fracture	1/463 (0.2%)	1
Upper limb fracture	1/463 (0.2%)	1
Investigations
Activated partial thromboplastin time prolonged	14/463 (3%)	19
Alanine aminotransferase increased	29/463 (6.3%)	35
Amylase increased	24/463 (5.2%)	37
Aspartate aminotransferase increased	40/463 (8.6%)	58
Bacterial test positive	3/463 (0.6%)	4
Bilirubin conjugated increased	1/463 (0.2%)	1
Blood albumin decreased	6/463 (1.3%)	10
Blood alkaline phosphatase decreased	1/463 (0.2%)	1
Blood alkaline phosphatase increased	49/463 (10.6%)	69
Blood bilirubin increased	9/463 (1.9%)	21
Blood calcium decreased	1/463 (0.2%)	1
Blood chloride decreased	8/463 (1.7%)	10
Blood creatine increased	1/463 (0.2%)	1
Blood creatinine decreased	2/463 (0.4%)	2
Blood creatinine increased	72/463 (15.6%)	152
Blood glucose increased	3/463 (0.6%)	4
Blood lactate dehydrogenase increased	11/463 (2.4%)	13
Blood lactic acid increased	2/463 (0.4%)	2
Blood magnesium decreased	6/463 (1.3%)	6
Blood potassium decreased	3/463 (0.6%)	3
Blood pressure increased	2/463 (0.4%)	3
Blood pressure orthostatic decreased	1/463 (0.2%)	1
Blood sodium decreased	4/463 (0.9%)	4
Blood sodium increased	1/463 (0.2%)	1
Blood urea decreased	1/463 (0.2%)	1
Blood urea increased	8/463 (1.7%)	8
Blood urine present	3/463 (0.6%)	3
Carbohydrate antigen 125 increased	1/463 (0.2%)	1
Eastern Cooperative Oncology Group performance status worsened	1/463 (0.2%)	1
Electrocardiogram QT prolonged	20/463 (4.3%)	34
Gamma-glutamyltransferase increased	44/463 (9.5%)	60
Glomerular filtration rate abnormal	1/463 (0.2%)	1
Glomerular filtration rate decreased	4/463 (0.9%)	5
Glomerular filtration rate increased	1/463 (0.2%)	1
Glucose tolerance test abnormal	1/463 (0.2%)	1
Glucose urine present	1/463 (0.2%)	1
Haemoglobin decreased	5/463 (1.1%)	14
Haemoglobin urine present	3/463 (0.6%)	4
Heart rate increased	3/463 (0.6%)	3
International normalised ratio increased	4/463 (0.9%)	7
Lymphocyte count decreased	29/463 (6.3%)	75
Lymphocyte count increased	1/463 (0.2%)	1
Mean cell volume increased	3/463 (0.6%)	3
Mean platelet volume decreased	1/463 (0.2%)	1
Neutrophil count decreased	39/463 (8.4%)	90
Neutrophil count increased	1/463 (0.2%)	1
Nitrite urine present	2/463 (0.4%)	2
Platelet count decreased	99/463 (21.4%)	232
Platelet count increased	2/463 (0.4%)	2
Protein total decreased	4/463 (0.9%)	4
Protein total increased	1/463 (0.2%)	1
Protein urine present	8/463 (1.7%)	12
Prothrombin time prolonged	4/463 (0.9%)	9
QRS axis abnormal	2/463 (0.4%)	2
Urine ketone body present	2/463 (0.4%)	2
Urine leukocyte esterase	1/463 (0.2%)	1
Urine leukocyte esterase positive	5/463 (1.1%)	9
Vitamin D decreased	1/463 (0.2%)	1
Weight decreased	43/463 (9.3%)	56
Weight increased	2/463 (0.4%)	2
White blood cell count decreased	55/463 (11.9%)	145
White blood cell count increased	1/463 (0.2%)	1
White blood cells urine positive	2/463 (0.4%)	2
Metabolism and nutrition disorders
Appetite disorder	2/463 (0.4%)	2
Decreased appetite	122/463 (26.3%)	142
Dehydration	42/463 (9.1%)	46
Electrolyte imbalance	1/463 (0.2%)	1
Gout	1/463 (0.2%)	2
Hypercalcaemia	7/463 (1.5%)	13
Hyperglycaemia	30/463 (6.5%)	61
Hyperkalaemia	8/463 (1.7%)	13
Hypermagnesaemia	3/463 (0.6%)	4
Hypernatraemia	2/463 (0.4%)	2
Hyperuricaemia	2/463 (0.4%)	2
Hypervolaemia	1/463 (0.2%)	1
Hypoalbuminaemia	21/463 (4.5%)	34
Hypocalcaemia	17/463 (3.7%)	21
Hypochloraemia	1/463 (0.2%)	1
Hypoglycaemia	1/463 (0.2%)	1
Hypokalaemia	40/463 (8.6%)	71
Hypomagnesaemia	77/463 (16.6%)	101
Hyponatraemia	50/463 (10.8%)	77
Hypophosphataemia	1/463 (0.2%)	1
Hypoproteinaemia	1/463 (0.2%)	1
Iron deficiency	1/463 (0.2%)	1
Malnutrition	3/463 (0.6%)	3
Musculoskeletal and connective tissue disorders
Arthralgia	23/463 (5%)	30
Back pain	47/463 (10.2%)	56
Chest wall mass	1/463 (0.2%)	1
Costochondritis	1/463 (0.2%)	1
Flank pain	8/463 (1.7%)	9
Groin pain	6/463 (1.3%)	6
Joint swelling	2/463 (0.4%)	2
Muscle spasms	15/463 (3.2%)	17
Muscle twitching	2/463 (0.4%)	2
Muscular weakness	19/463 (4.1%)	20
Musculoskeletal chest pain	11/463 (2.4%)	13
Musculoskeletal pain	12/463 (2.6%)	12
Musculoskeletal stiffness	1/463 (0.2%)	1
Myalgia	17/463 (3.7%)	22
Neck pain	9/463 (1.9%)	9
Osteoarthritis	1/463 (0.2%)	1
Pain in extremity	15/463 (3.2%)	15
Pain in jaw	3/463 (0.6%)	3
Spondylitis	1/463 (0.2%)	1
Trismus	2/463 (0.4%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to breast	1/463 (0.2%)	2
Ovarian cancer metastatic	1/463 (0.2%)	2
Nervous system disorders
Akathisia	1/463 (0.2%)	1
Amnesia	1/463 (0.2%)	1
Anosmia	2/463 (0.4%)	2
Aphasia	1/463 (0.2%)	1
Ataxia	1/463 (0.2%)	1
Balance disorder	3/463 (0.6%)	3
Cognitive disorder	2/463 (0.4%)	2
Coordination abnormal	1/463 (0.2%)	1
Dizziness	50/463 (10.8%)	61
Dizziness postural	1/463 (0.2%)	1
Dysgeusia	20/463 (4.3%)	22
Extrapyramidal disorder	1/463 (0.2%)	1
Headache	87/463 (18.8%)	109
Hypoaesthesia	5/463 (1.1%)	11
Hypogeusia	1/463 (0.2%)	1
Hyposmia	2/463 (0.4%)	2
Lethargy	1/463 (0.2%)	1
Loss of consciousness	1/463 (0.2%)	1
Loss of proprioception	1/463 (0.2%)	1
Memory impairment	4/463 (0.9%)	4
Migraine	1/463 (0.2%)	1
Monoplegia	1/463 (0.2%)	1
Neuralgia	1/463 (0.2%)	1
Neuropathy peripheral	14/463 (3%)	14
Paraesthesia	4/463 (0.9%)	5
Parosmia	1/463 (0.2%)	2
Peripheral sensory neuropathy	7/463 (1.5%)	7
Post-traumatic headache	1/463 (0.2%)	1
Presyncope	1/463 (0.2%)	1
Restless legs syndrome	1/463 (0.2%)	2
Sciatica	2/463 (0.4%)	2
Secondary cerebellar degeneration	1/463 (0.2%)	1
Sinus headache	2/463 (0.4%)	2
Somnolence	2/463 (0.4%)	2
Syncope	4/463 (0.9%)	4
Tremor	5/463 (1.1%)	5
Vocal cord paralysis	1/463 (0.2%)	1
Product Issues
Device occlusion	1/463 (0.2%)	1
Psychiatric disorders
Abnormal dreams	1/463 (0.2%)	1
Anxiety	36/463 (7.8%)	44
Confusional state	11/463 (2.4%)	11
Depression	17/463 (3.7%)	19
Insomnia	98/463 (21.2%)	117
Mania	1/463 (0.2%)	1
Mental status changes	2/463 (0.4%)	2
Nervousness	1/463 (0.2%)	1
Restlessness	1/463 (0.2%)	1
Suicidal ideation	1/463 (0.2%)	1
Renal and urinary disorders
Acute kidney injury	3/463 (0.6%)	3
Bladder discomfort	1/463 (0.2%)	1
Bladder spasm	1/463 (0.2%)	1
Chromaturia	1/463 (0.2%)	1
Chronic kidney disease	5/463 (1.1%)	13
Dysuria	8/463 (1.7%)	8
Glycosuria	1/463 (0.2%)	1
Haematuria	12/463 (2.6%)	13
Hydronephrosis	6/463 (1.3%)	6
Incontinence	2/463 (0.4%)	2
Micturition urgency	6/463 (1.3%)	6
Pollakiuria	7/463 (1.5%)	7
Proteinuria	12/463 (2.6%)	17
Renal failure	2/463 (0.4%)	2
Renal impairment	1/463 (0.2%)	1
Renal pain	1/463 (0.2%)	1
Ureteric obstruction	1/463 (0.2%)	1
Urethral pain	1/463 (0.2%)	1
Urinary hesitation	2/463 (0.4%)	2
Urinary incontinence	5/463 (1.1%)	5
Urinary retention	2/463 (0.4%)	2
Urinary tract pain	3/463 (0.6%)	3
Urine abnormality	1/463 (0.2%)	2
Urine odour abnormal	2/463 (0.4%)	2
Urogenital disorder	1/463 (0.2%)	1
Reproductive system and breast disorders
Adnexa uteri pain	1/463 (0.2%)	2
Atrophic vulvovaginitis	1/463 (0.2%)	1
Breast disorder	1/463 (0.2%)	3
Breast mass	1/463 (0.2%)	1
Breast pain	3/463 (0.6%)	3
Breast swelling	1/463 (0.2%)	1
Cystocele	1/463 (0.2%)	1
Nipple pain	1/463 (0.2%)	2
Pelvic discomfort	1/463 (0.2%)	2
Pelvic pain	3/463 (0.6%)	4
Vaginal discharge	5/463 (1.1%)	5
Vaginal disorder	1/463 (0.2%)	1
Vaginal haemorrhage	6/463 (1.3%)	7
Vulvovaginal discomfort	2/463 (0.4%)	2
Vulvovaginal dryness	1/463 (0.2%)	1
Vulvovaginal erythema	1/463 (0.2%)	1
Vulvovaginal pain	1/463 (0.2%)	1
Vulvovaginal pruritus	2/463 (0.4%)	3
Respiratory, thoracic and mediastinal disorders
Cough	60/463 (13%)	65
Dysphonia	5/463 (1.1%)	5
Dyspnoea	85/463 (18.4%)	100
Dyspnoea at rest	1/463 (0.2%)	1
Dyspnoea exertional	9/463 (1.9%)	9
Epistaxis	22/463 (4.8%)	27
Haemoptysis	2/463 (0.4%)	2
Hiccups	2/463 (0.4%)	2
Nasal congestion	10/463 (2.2%)	13
Nasal discomfort	1/463 (0.2%)	1
Oropharyngeal pain	20/463 (4.3%)	22
Painful respiration	1/463 (0.2%)	1
Paranasal sinus hypersecretion	1/463 (0.2%)	1
Pleural effusion	17/463 (3.7%)	21
Pleuritic pain	1/463 (0.2%)	1
Productive cough	7/463 (1.5%)	8
Pulmonary embolism	3/463 (0.6%)	3
Pulmonary pain	1/463 (0.2%)	2
Respiratory depression	1/463 (0.2%)	1
Respiratory disorder	1/463 (0.2%)	1
Respiratory distress	1/463 (0.2%)	1
Respiratory tract congestion	2/463 (0.4%)	2
Rhinitis allergic	6/463 (1.3%)	6
Rhinorrhoea	8/463 (1.7%)	11
Sinus congestion	4/463 (0.9%)	4
Sinus disorder	1/463 (0.2%)	1
Sputum increased	1/463 (0.2%)	1
Throat irritation	1/463 (0.2%)	1
Upper-airway cough syndrome	3/463 (0.6%)	3
Wheezing	3/463 (0.6%)	3
Skin and subcutaneous tissue disorders
Acne cystic	1/463 (0.2%)	1
Alopecia	16/463 (3.5%)	16
Blood blister	1/463 (0.2%)	1
Cold sweat	1/463 (0.2%)	1
Dry skin	6/463 (1.3%)	6
Ecchymosis	2/463 (0.4%)	3
Eczema	1/463 (0.2%)	1
Erythema	1/463 (0.2%)	1
Hyperhidrosis	6/463 (1.3%)	6
Madarosis	1/463 (0.2%)	1
Nail discolouration	1/463 (0.2%)	1
Night sweats	7/463 (1.5%)	7
Onychoclasis	1/463 (0.2%)	1
Pain of skin	1/463 (0.2%)	1
Petechiae	8/463 (1.7%)	8
Photosensitivity reaction	4/463 (0.9%)	4
Pruritus	9/463 (1.9%)	10
Purpura	4/463 (0.9%)	4
Rash	19/463 (4.1%)	22
Rash erythematous	1/463 (0.2%)	1
Rash maculo-papular	5/463 (1.1%)	7
Rash pruritic	1/463 (0.2%)	1
Skin exfoliation	1/463 (0.2%)	1
Skin hyperpigmentation	1/463 (0.2%)	1
Skin lesion	1/463 (0.2%)	1
Skin mass	1/463 (0.2%)	1
Skin tightness	1/463 (0.2%)	1
Skin ulcer	1/463 (0.2%)	1
Urticaria	2/463 (0.4%)	2
Surgical and medical procedures
Tooth extraction	1/463 (0.2%)	2
Vascular disorders
Angiopathy	1/463 (0.2%)	1
Deep vein thrombosis	3/463 (0.6%)	3
Embolism	2/463 (0.4%)	2
Flushing	4/463 (0.9%)	4
Haematoma	2/463 (0.4%)	2
Hot flush	20/463 (4.3%)	21
Hypertension	55/463 (11.9%)	84
Hypotension	5/463 (1.1%)	6
Lymphoedema	1/463 (0.2%)	1
Orthostatic hypotension	1/463 (0.2%)	1
Peripheral coldness	1/463 (0.2%)	1
Thrombosis	2/463 (0.4%)	2
Venous occlusion	1/463 (0.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.